Process for the manufacture of
bipyridyls



United States Patent 3,272,836 PROCESS FOR THE MANUFACTURE OF BIPYRKDYLS Roy Duffy and Alexander Hunter McQuillan, Widnes,

England, assignors to Imperial Chemical industries Limited, London, England, a corporation of Great Britain No Drawing. Filed Nov. 6 1963, Ser. No. 321,678 Claims priority, application Great Britain, Nov. 12, 1962, 42,617/62 11 Claims. (Cl. 260-496) This invention relates to the manufacture of organic bases and more particularly of bipyridyls.

In U.S. Patent 3,210,360, to Bradbury et a1. there is described a process for the manufacture of bipyridyls which comprises interacting magnesium and a pyridine and oxidising the interaction product so formed.

In these processes, the yield of bipyridyle falls considerably short of that theoretically obtainable from the pyridine employed. As pyridines are relatively expensive materials, it is clearly desirable to increase the efficiency of conversion of pyridine to the desired bipyridyls.

We have now found that valuable improvements in the yield can be obtained by carrying out the oxidation and interaction together.

Thus according to our invention we provide an improved process for the manufacture of bipyridyls which comprises interacting a metal and a pyridine in the pres ence of an oxidising agent.

The metal may be any metal which is reactive towards the pyridine, provided that the interaction between the metal and the oxidising agent in the reaction mixture is not likely to take place preferentially or violently. The suitability of any particular metal will depend, of course, upon the particular combination of metal, pyridine and oxidising agent to be employed and the relative reactivity of the various components towards each other, but may be determined by simple trial. Magnesium is an especially suitable metal for use in our process.

The metal may be used conveniently as a substantially pure metal, but alloys may be used if desired. The metal may be used in any convenient form, preferably one having a large surface area, for example turnings, granules, powder or foil. The surface of the metal should be as clean as possible to facilitate reaction.

The pyridine for use in the process of the present invention should be as free as possible from any substituent or impurity (for example pipe-ridine) which can take part in any undesirable side-reaction with the metal or the initiator. The process is especially applicable to pyridine itself. Pyridines containing hydrocarbon radicals (particularly alkyl radicals, for example methyl and/or ethyl radicals) may also be used, for example picolines and lutidines, but these are usually less reactive than pyridine itself.

The oxidising agent is preferably one which is substantially anhydrous and which does not preferentially attack the metal. Suitable oxidising agents include oxygen and mixtures thereof with an inert diluent such as nitrogen, and conveniently air. Such a gaseous oxidising agent, which should preferably be substantially dry, is conveniently blown or bubbled through a mixture of the metal and the pyridine, optionally containing a diluent. An especially convenient oxidising agent is an organic nitro compound. This has the advantage that it appears to be less liable to interfere with the interaction, and so may be added to the interacting metal-pyridine mixture in proportion in excess of that required for the oxidation, but Wl'tllOlllZ interfering with the interaction. The excess of nitro compound serves as a useful diluent and solvent for the reaction products, primarily the bipyridyls.

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Suitable nitro compounds include nitro derivatives of aromatic hydrocarbons, for example nitrobenzene and nitroalkanes, for example nitromethane and nitroethane. The nitroalkanes are preferred, as they tend to form gaseous or volatile by-products which are more easily removed from the reaction mixture than the by-products formed from aromatic nitro compounds.

The process is preferably carried out by adding the oxidising agent to an interacting mixture of metal and pyridine. This is especially so when the oxidising agent is a nitroalkane. The rate of addition of the oxidising agent may, in some cases, need to be controlled so as to avoid interference with the interaction, but in general it is sufficient to add the oxidising agent at a rate which maintains a small proportion of metal-pyridine interaction product (which can usually be noticed by its blue-black colour) in the reaction mixture. This technique minimises the risk of prematurely quenching the interaction before the reaction mixture is ready for isolation of the product.

The total amount of oxidising agent to be used is often rather difficult to calculate in view of the variety of reactions which can occur. In general, we find that it is best to use a proportion which is sufficient to discharge the characteristic (blue-black) colour of the metal-pyridine interaction product. If the colour is difiicult to discern, it is usually sufficient to add oxidising agent until no more reaction is evident, for example as shown by heat evolution.

The interaction of metal and pyridine may be slow to start. In the case of magnesium, reaction may be started by addition of a small proportion of an initiator, particularly a material which can induce the formation of free radicals in the interaction mixture, for example alkali metals (e.g. lithium, sodium or potassium) and the halogens (particularly bromine and iodine). The alkali metals are best used in finely divided form, for example as a dispersion in an inert diluent. An alkyl halide or a quaternary pyridinium salt may be used also. The interaction is preferably initiated by addition of a suitable initiator before any oxidising agent is present, though in those cases in which the initiator and the oxidising agent do not themselves interact to any appreciable degree, the initiator may be added in the present of the oxidising agent if desired. Interaction of the metal and pyridine can be initiated satisfactorily by the alkyl halide or quaternary pyridinium salt, in the presence of an aromatic nitro compound if desired, provided that the proportion of nitro compound is not greater than about 0.08 mole and preferably not greater than 0.06 mole per mole of pyridine The interaction and oxidation are preferably carried out at a temperature in the range about 90 C. up to the boiling point of the mixture. Higher and lower temperatures may be used if desired, though temperatures below C. may be inconveniently slow. It is usually adequate to carry out the reaction at substantially atmospheric pressure, though higher or lower pressures may be used if desired. In general, a temperature in the range C. to 120 C. gives the best combination of speed and efficiency. In the case of gaseous oxidants, care should be taken that the reaction conditions are not likely to give rise to explosive mixtures in the reaction vessel, and in particular that reaction is carried out at a temperature at which any gaseous mixtures likely to be formed (for example an air-pyridine mixture) do not inflame. For this reason, it is necessary to carry out the process at a temperature above C. when oxygen is used as oxidant. In the case of liquid oxidants, however, this restriction may not apply.

Commonly a mixture of isomeric bipyridyls is produced by the process of our invention, the principal constituents being the 2:2-, 2:4- and 4:4'-isomers, or such of these as are permitted by the structure of the pyridine used as starting material. The 4:4-isomer usually predominates.

The bipyridyls, which are useful as intermediates for chemical synthesis and for the manufacture of herbicidal materials, may be isolated from the reaction mixture by known methods. Thus for example there may be used fractional distillation (particularly under reduced pressure), fractional crystallisation, extraction with organic solvents, or combinations of such techniques. The method to be used may vary according to whether the product desired is the mixture of all the bipyridyls produced in the reaction, or particular isomers. In general, the bipyridyls can be freed first from most of the excess pyridine and any volatile diluent used by a preliminary distillation at atmospheric pressure, and then from terpyridyls and other materials by fractional distillation under reduced pressure. If desired, the reaction mixture may be extracted with a solvent in order to eliminate any metal hydroxide present, before or after any preliminary distillation, and this solvent then removed by distillation; suitable solvents for this purpose include methylene chloride and benzene.

The invention is illustrated but not limited by the following examples in which the parts and percentages are by weight.

Example 1 A mixture of 12 parts of magnesium turnings and 395 parts of dry pyridine was heated to boiling and interaction was initiated by addition of 14 grams of a allyl bromide. The mixture was then maintained at approximately 115 C. for 60 minutes while a stream of oxygen was blown through the mixture at a rae of 200 ml. of per minute for each 12 grams of magnesium. Analysis of the reaction product then showed that the mixture contained 33.5 grams of 4:4'-bipyridyl, representing a conversion efiiciency of 59% of theory based on the pyridine consumed.

Example 2 A mixture of 12 parts of magnesium granules (1 mm. size) and 395 parts of dry pyridine was heated to boiling and interaction was initiated by addition of parts of allyl chloride. The mixture was then maintained at 116 C. for 120 minutes while a steam of oxygen was blown through the mixture at a rate of 200 ml. of per minute for of magnesium. Analysis of the reaction product showed that the mixture contained 23 parts of 4:4'-bipyridyl, representing a conversion efficiency of 60.5% of theory based on the pyridine consumed.

Example 3 A mixture of 395 parts of redistilled pyridine (water content less than 0.01%) and 12 parts of magnesium (1 mm. graules) was heated to 70 C. and interaction was initiated by addition 5.4 parts of a sodium dispersion containing 25% of sodium metal in trimethylbenzene and heating the mixture to boiling. Three minutes after initiation of interaction, nitroethane was added in portions (each of 1.1 parts) at 3 minute intervals until a total of 31.9 parts had been added. The mixture was then cooled to about 60 C. and 64 parts of methanol were added to reduce its viscosity. Analysis of the product showed the presence of 34.3 parts of 4:4'-bipyridy1, representing a conversion efficiency of 53% of therory based on the pyridine consumed.

Example 4 The procedure of Example 3 was repeated, except that the addition of nitroethane was made in portions (each of 1.1 parts) at 3 minute intervals until a total of 11 parts had been added and then at 6 to 7 minute intervals until a total of 28.6 parts had been added. Analysis of the product showed the presence of 33.6 parts of 4:4-bipyridyl repersenting a conversion efiiciency of 53% based on the pyridine consumed.

What we claim is:

1. In a process for the manufacture of a bipyridyl by the reaction of a metal and a pyridine to form a metalpyridine interaction product and oxidation of said inter action product to bipyridyl, the improvement which comprises carrying out siad reaction and oxidation simultaneously.

2. Process as claimed in claim 1 wherein the metal is magnesium.

3. Process as claimed in claim 2 wherein the pyridine is "pyridine itself.

4. Process as claimed in claim 1 wherein the oxidation is effected by means of a substantially anhydrous oxidising agent which does not preferentially attack said metal.

5. Process as claimed in claim 4 wherein the oxidising agent is oxygen.

6. Process as claimed in claim 4 wherein the oxidising agent is an organic nitro compound.

7. Process as claimed in claim 6 wherein the oxidising agent is a nitroalkane.

8. Process as claimed in claim 4 wherein the reaction between the metal and the pyridine is initiated before any oxidising agent is added to the reaction mixture.

9. Process as claimed in claim 1 wherein the temperature employed is in the range C. to 120 C.

10. In a process for the manufacture of a bipyridyl by the reaction of a metal and a pyridine to form a metalpyridine interaction product and oxidation of said interaction product to bipyridyl, the improvement which comprises forming a reaction mixture of magnesium and pyridine, heating said mixture to a temperature in the range of C. to C., and adding substantially anhydrous oxygen to said reaction mixture as the reaction proceeds between the magnesium and pyridine, the amount of oxygen added being sufficient to discharge the color of the magnesium-pyridine reaction product.

11. In a process for the manufacture of a bipyridyl by the reaction of a metal and a pyridine to form a metalpyridine interaction product and oxidation of said interaction product to bipyridyl, the improvement which comprises forming a reaction mixture of magnesium and pyridine, heating said mixture to a temperature in the range of 90 C. to 120 C., and adding a substantially anhydrous lower nitroalkane to said reaction mixture as the reaction proceeds between the magnesium and pyridine, the amount of lower nitroalkane added being sufiicient to discharge the color of the magnesium-pyridine reaction product.

No references cited.

WALTER A. MODANCE, Primary Examiner.

ROBERT T. BOND, Assistant Examiner. 

1. IN A PROCESS FOR THE MANUFACTURE OF A BIPYRIDYL BY THE REACTION OF A METAL AND A PYRIDINE TO FORM A METALPYRIDINE INTERACTION PRODUCT AND OXIDATION OF SAID INTER ACTION PRODUCT TO BIPYRIDYL, THE IMPROVEMENT WHICH COMPRISES CARRYING OUT SAID REACTION AND OXIDATION SIMULTANEOUSLY. 